The major goal of this project is to investigate the molecular mechanism of specific cell-cell adhesion among embryonic cells from a variety of vertebrate tissues. Our approach will involve four main objectives: 1) a quantitative description of the adhesion process at the single cell level in terms of its kinetics and specificity, 2) the isolation and extensive characterization of endogenous substances that can affect adhesion, 3) a study of the surface membranes of embryonic cells with respect to the presence and distribution of molecules involved in cell-cell binding, 4) the use of single cell methods to identify molecular events in cell-cell binding and to test specific models for the mechanism of adhesion. These studies will combine a variety of techniques in protein biochemistry, in vitro tissue culture, immunology, cell fractionation, cell surface mapping, and single cell manipulation. A key aspect of this methodology will be the application of fiber fractionation procedures developed in our laboratory for the observation and quantitation of individual cell-cell binding events between single cells, and the analysis of cell-substrate interactions. Of particular value in this method is the ability to quantitate binding between different cell types without ambiguity, and to examine the effect of various reagents on one or both cells in each binding event. Our experiments will utilize tissues from both chickens and mice. With inbred mice, it is anticipated that our studies will be facilitated by the ability to do genetic studies and to use well characterized cell lines. In addition it is hoped that results obtained with mammals will have greater relevance to problems in human development.